Three new types of enzyme inactivators will be synthesized and evaluated. These inactivators are relatively unreactive molecules which are converted to reactive species through the catalytic action of the enzymes. The general structure of the inactivators and the target enzymes are: 1) R-CF2CHNH3 positive COO negative transaminases, aminoacid decarboxylases; 2) R-CF2CH2COSCoA-crotonase, propionyl-CoA carboxylase, transcarbosylase; 3) Cyclopropane derivatives - proteolytic enzymes, esterases. If these compounds are sufficiently active in vitro, their in vivo effect will be examined. These compounds could be used as drugs and to produce animal models for genetic diseases. The mechanism of action of these enzymes will be investigated: 1) B12-coenzyme dependent enzymes. How does the protein catalyze cleavage of the C-Co bond? 2) Plasma amine oxidase - structure of the active site. 3) Gamma-cystathionase - mechanism by which two of the subunits are "turned off" when two are occupied by an inactivator. 4) Proline racemase. Is the active site at the intersection of two subunits? 5) Phosphopantotheine decarboxylase. The decarboxylation is unusual since there is no electron sink. We will investigate the mechanism of this decarboxylation.